Process for the preparation of isomaleimides



United States Patent 2,995,577 PROCESS FOR THE PREPARATION OF ISOMALEIMIDES Carol K. Sauers, Middlebush,.and Robert I. Cotter, New

Brunswick, NJ., assignors to Union Carbide Corporation, a corporation of New York No Drawing. Filed Nov. 5, 1959, Ser. No. 851,027

' 9' Claims. (Cl. 260-'343.6)

This invention relates to isomaleimides. More particularly, this invention relates to a process for the preparation of N-substituted isomaleimides.

The N-substitu-ted isomaleimides which can be prepared in accordance with the present invention have the general formula:

0 i an These latter N-substituted isomaleimides are commonly referred to as bis-isomaleimides.

The term monovalent hydrocarbon radical as used herein refers to substituted hydrocarbon radicals as well as unsubstituted hydrocarbon radicals.

Exemplary of such radicals are the following: alkyl radicals, such as methyl, ethyl, n-propyl, n-butyl, n-hexyl, 2- ethyl-n-hexyl, n-octyl, n-dodecyl, ,and the like; cycloalkyl radicals, such as cyclohexyl and the like; unsaturated alkyl and cycloalkyl radicals, such as allyl, cyclopentenyl, and the like; halogenated alkyl and cycloalkyl radicals, such as chloroethyl, bromoethyl, fluoroethyl, 2-chloro-npropyl, 2-bromo-n-propyl, 2-chloro-n-butyl, 3-chloro-namyl, 3-bromo-n-amyl, 2-chloro-n-hexyl, 2-chlorocyclohexyl, and the like; alkoxy and aryloxy substituted alkyl and cycloalkyl radicals, such as methoxymethyl, ethoxyethyl, 3 ethoxy-n-propyl, 4-ethoxy-n-butyl, 3-ethoxy-2- ethyl-n-hexyl, 2-methoxycyclohexyl, phenoxymethyl, 2- phenoxyethyl, 3-phenoxy-n-propyl, 2-pheno'xy cyclohexyl, and the like; aralkyl radicals, such as benzyl, 2-phenyl ethyl,'-3-phenyl-n-propyl, l-ph'enyl-n-butyl, l-phenyl-n-docesyl, and the like; aryl radicals, such as phenyl, naphthyl, and the like; halogenated aryl radicals, such as p-chlorophenyl, p-bromophenyl, p-fluorophenyl, p-iodophenyl, 2- chloronaphthyl, 2-bromonaphthyl, and the like; alkoxy and aryloxy substituted aryl radicals, such as p-methoxyphenyl; p-ethoxyphenyl, p-n-propoxyphenyl, and the like; alkaryl radicals, such as o-methylphenyl, p-ethylphenyl, pn-propylphenyl, o-n-propylphenyl, o-n-butylphenyl, pndodecylphenyl, p-(2-ethyln-hexyl)phenyl, andthe like; nitro substituted aryl radicals, such as p-nitrophenyl, 2- nitronaphthyl, and the like; other suitable radicals include 4-hydroxy-1-naphthyl, and the like.

Representative of isomaleimides wherein R in the general formula previously given is a monovalent hydrocarbon radical are the following: N-methyl isomaleimide, N-ethyl isomaleimide, N-n-propyl isomaleimide, N-allyl isomaleimide, n-butyl isomaleimide, N-tertiary butyl isomaleimide, N-n-hexyl isomaleimide, N-(Z-ethyln-hexyl) isomaleimide, N-n-heptyl isomaleimide, N-nnonyl isomaleimide, N-n-dodecyl isomaleimide, N- n-docosyl isomaleimide, N-cyclohexyl isomaleimide, N-

Patented Aug. 8, 1961 '2 (2-chloroethyl) isomaleimide, N-(2-bromoethyl) isomaleimide, N-(2-fluoroethyl) isomaleimide, N-(2-i0do-npropyl) isomaleimide, N-(2-chloro-n-hexyl) "isomaleimide, N-methoxymethyl isomaleimide, N-benzyl isomaleimide, N-(Z-phcnylethyl) isomaleimide, N-(3-phenyl-npropyl) isomaleimide,N-(4-phenyl-n-butyl) isomaleimide, N-phenyl isomaleimide, N-naphthyl isomaleimide, N-(ochlorophenyl) isomaleimide, :N-(m-bromophenyl) isomaleimide, N-(p-fluorophenyl) isomaleimide, N-(o-iodophenyl) isomaleimide, N-(o-methoxyphenyl) isomaleimide, N-(m-methoxyphenyl) isomaleimide, N-(p-ethoxyphenyl) isomaleimide, N-(p-n-butoxyphenyl) isomaleimide, N-(p-chloro-m-methylphenyl) isomaleimide, N-(o-methylphenyl) isomaleimide, N-(m-methylphenyl) isomaleimide, N-(o-ethylphenyl) isomaleimide, N-(methylphenyl) isomaleimide, N-(p-ethylphenyl) isomaleimide, N-(o-isopropylphenyl) isomaleimide, N-(m-iso propylphenyl) isomaleimide, N-(p-isopropylphenyl) isomaleimide,, N-(o-n-butylphenyl) isomaleimide, N-(m-nbutylphenyl) isomaleimide, N-(4-hydroxy-2-naphthyl) isomaleimide, N-(4-hydroxy-1-naphthyl) isomaleimide, and the like.

The term divalent hydrocarbon radical as used herein is intended to encompass both unsubstituted as well as substituted divalent hydrocarbon radicals. Illustrative of suitable radicals are alkylene radicals, such as ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, 2-ethyl hexamethylene, octamethylene, nonamethylene, decamethylene, and the like; the cycloaliphatic radicals, such as 1,4-cyclohexane, 1,3-cyclohexane, 1,2- cyclohexane, and the like; halogenated alkylene and cycloaliphatic radicals, such as 2-chloroethylene, 2-bromoethylene, 2 lluoroethylene, 2-iodoethylene, 2-chlorotrimethylene, 2-bromotrimethylene, Z-chloropentamethylene, 3-chlorohexamethylene, Z-chlorooctamethylene, and the like; alkoxy and aryloxy substituted alkylene and cycloaliphatic radicals, such as methoxy methylene, ethoxy methylene, ethoxy ethylene, 2-ethoxy trimethylene, 3- ethoxy pentamethylene, 1,4 (Z-methoxy cyclohexane), phenoxy ethylene, 2-phenoxy trimethylene, 1,3-(2-phenoxy cyclohexane), and the like; aralkylene radicals, such as phenyl ethylene, Z-phenyl trimethylene, l-phenyl pentamethylene, Z-phenyl decamethylene, and the like; aromatic radicals, such as phenylene, naphthylene, and the like; halogenated aromatic radicals, such as 1,4-(2-chlorophenylene), 1,4-(2 bromophenylene), 1,4 (2-fluorophenylene), and the like; alkoxy and aryloxy substituted aromatic radicals, such as 1,4-(2-methoxyphenylene), 1,4- (2-ethoxypheny1ene) 1,4 (2-n-propoxyphenylene) l ,4- (Z-phenoxyphenylene), and the like; alkyl substituted aromatic radicals, such as 1,4-(2-methylphenylene), 1,4-

,. (Z-ethylphe'nylene), 1,4-(2-n-propylphenylene), 1,4-(2- n-butylphenylene), 1,4-(2-n-dodecylphenylene), and the like.

Among N-substituted isomaleimides wherein R in the formula previously noted is a divalent hydrocarbon radical having as a substituent on its terminal carbon atom a radical having the formula:

maleimid'e, N,N'-(l-ethoxytetramethylene) bis-isomaleimide, N,N'-[1,4-(Zmethoxycyclohexane)] bis-isomaleimide, N,N -(2-phenoxyethylene) bis-isomaleimide, N,

Particularly desirable halogenated acid anhydrides are those compounds wherein R and R each contains a maximum of 10 carbon atoms. Representative radicals for R and R include, among others, monochloromethyl,

N-(2-phenoxytrimethylene) bis-isomaleimide, N,N-[1, 5 dichloromethyl, trichloromethyl, monobromomethyl, di- 4-(21 phenoxycyclohexane)] bis-isomaleimide, N,N'-[l, "bromomethyl, 'tribromomethyl, monofluoromethyl, di- 4-(2-nitrocyclohexane)] bis-isomaleirnide, N,N'-phenylfiuoromethyl, trifluorornethyl, mono-iodomethyl, di iodoethylene bis-isomaleimide, N,N-(2-pheny1ethylene) bismethyl, tri-iodomethyl, a,a-dichloroethyl, ,z-dibromoisomaleimide, N,N'-(2-phenyltrimethylene) bis-isomaleethyl, a,a-difluoroethyl, u,a-diiodoethyl,' a-chloro-n-propyl, imide, N,N-(2-phenyltetramethylene) bis-isornaleimide, a-bromo-n-propyl, u-fluoro-n-propyl, a-iodon-propyLmp- N,N-(l-phenyldodecamethylene) bis-isomaleimide, N, dichloroethyl, a,fl-dibromoethyl, a,B-difluoroethyl, 0:,B-di- N-(1,4-phenylene) bis-isomaleimide, N,N-(1,5-naphiodoethyl, a,'y-dichloro-n-amyl, ayy-dibromo-n-amyl, ath-alene) bis-isomaleimide, N,N-[1,4-(2-chlorophenylchlorodecyl, a,fi-dichlorodecyl, a,y-dibromodecyl. Speene)] bis-isomaleimide, N,N'-[1,4:(2-bromophenylene)]' cific compounds include, among others, brornoacetic anbis-isomaleirnide, N,N'-[1,4-(2-methoxyphenylene)] bishydride, trifluoroacetic anhydride, acetic anhydnde, isomaleimide, N,N-[1,4-(2-ethoxyphenylene)] bis-isodichloroacetic anhydride, dibromoaoetic anhydride, trimaleimide, N,N'-[1,4-(2-phenoxyphenylene)] bis-isofluoroacetic anhydride, a,fi-di-fluoroacetic anhydride, 11,0:- maleimide, N,N'-[l,4-(2-methylphenylene)] bis-isomaledichloropropionic anhydride, a,fi-dibromopropionic animide, N,N-[1,4-(2-ethylphenylene)] bis-isomaleimide, hydride, trifluoroacetyl-u-chloropropionate, chloroacetyl- N,N'-(4,4-diphenyl methane) bis-isomaleimide, N,N'- a-bromobutyrate, bromoacetyl-a,a difluoropropionate, (4,4'-diphenylether) bis-isomaleimide, N,N'-[1,4 2 nand the like. dodecylphenylene)] bis-isomaleimide, N,N-(4,4-benzo- Any of the organic tertiary amines can be used for phenone) bis-isomaleimide, and the like. P p of the P t invention Particularly Preferred Particularly desirable compounds for purposes of this are the'organic tertiary amines which are free of interferinvention are those wherein R is either a monovalent or ing groups such as COOH and NH having a maxidivalent radical as previously described having a maxi-' mum of 20 carbon atoms and also being free of olefinic mum of 20 carbon atoms and being free of interfering and acetylel1i0 unsaturation- Among Suitable rga groups such as COOH nd NH tertiary amines can be noted trimethylamine, triethyl- In its broadest aspect, the process by which the N- amine, tri-n-propylamine, tri-n-butylamine, tri-n-amylsubstituted isomaleimides of the present invention are amine, tri-n-hexylamine, tri-(Z-ethyl-n-hexyDamine, triprepared is conducted by admixing an N-substituted malen-heptyl'amine, dimethylbutylamine, methylhexylpropylamic acid having the general formula: amine, N-methyl-N-hexyl aniline, N,N-dimethyl-p-ethoxy O aniline, N-methyl morpholine, N-ethyl morpholine, N,N-

dimethyl am'sidine, Z-chIoropyridine, 4-chloropyridine, a5 quinuclidin'e, quinoline, N,N-dimethyl piperazine, and H the like.

h'Ihe preparation of an N-substituted isomaleimide w erein R is a monovalent hydrocarbon radical as pre- "i which R 15 a g i f g i i' viously described can be illustrated by the reaction of a vlously defitied f i i rocaI i 40 mixture containing N-n-butyl maleamic acid, trifluoroas preylous y e or T s acetic anhydride, and triethylamine. This reaction can on its terminal carbon atom a ra ica avingt e orrnu a. be represented by the following equafi 0113:,

mc-o=o HO 0 c H 46 ll OHMCIH') f" f nc-u-mn F:CC=O

with a halogenated acid anhydride and an organic tertiary amine. dn h 50 The term halogenated acid anhy 'de as used erein is intended to encompass those compounds having the 0+2[NH(CH)]++2[F'G C"O1 formula:

ra-0:0 C4Ho 0 The preparation of an N-substimted isomaleimide wherein R is a divalent hydrocarbon radical having as a RL'C=O substituent on its terminal carbon atom the radical prein which R2 and R3 are alkyl radicals having the Same viously noted can be illustrated by the reaction of a mixor different number of carbon atoms and wherein both of ture containing N,N'-(4,4'-diphenylmethane) bis-malethe alkyl radicals have at least one halogen atom, i.e., amic acid, trifluoroacetic anhydride, and triethylamine. chlorine, fluorine, bromine, or iodine, attached to the This reaction can be represented by the following equaon carbon atom, i.e., the carbon attached to -C=O. tions: W

O o 0 A I ll F10- H-O- OH OH-CC-H H I FsC-C O H O 0 II E HCC\ -0 it o o a HlNH(CzH4)|1*+ [Fac-0= l' H- O C- H Various amounts of the different starting materials can be used. Generally, it is preferred to use at least about a stoichiometric amount of. the halogenated acid anhydride. Using more than a stoichiometric amount can be used if so desired, but it is economically undesirable. For purposes of stoichiometric calculations, one acid anhydride group:

is deemed to react with one carboxylic acid group COOH. The organic tertiary amine is also used in at least stoichiometric amounts. If desired, however, more than a stoichiometric amount can be used, but again this is economically unattractive. For purposes of stoichiometric calculations, two amine groups.

are comidered to react with one anhydride group:

The temperature at which the process of thepresent invention is conducted can be varied over a wide range, from as low as 70 C. to a temperature just below the decomposition temperature of the reactants and of the iso- -maleimide product formed. At temperatures lower than about 70 C., the reaction proceeds sluggishly. A temperature in the range of about C. to about 85 C. is most preferred.

It is also preferred to conduct the present process in the presence of an organic diluent which is a solvent for the starting materials and is non-reactive with respect to the starting materials and the final product.

The reaction involved in the instant process is exothermic. If an organic diluent is not present, it may be difiicult to remove the heat of reaction, which, if not removed, might cause undesirable side reactions to occur. In addition, the use of an organic diluent facilitates removal of the N-substituted isomaleimide from the starting materials.

The actual organic diluent used will depend upon the starting materials and the temperature at which the reaction is to be conducted. The organic diluent should have a boiling point at or above the reaction temperature. It is customary to use the organic diluent in amounts of at least about 50% by weight based on the weight of the starting materials. The upper limit with respect to the amount of organic diluent used will depend upon the rate at which it is desired to conduct the reaction. The more dilute the reaction mixture, the slower the rate of reaction. From a practical standpoint, the organic diluent -is used in amounts up to about 500% by weight based on the weight of the starting materials.

Suitable organic diluents include, among others, the aromatic hydrocarbons, such as benzene, xylene, and the like; the halogenated aromatic hydrocarbons, such as chlorobenzene and the like; cycloaliphatic hydrocarbons,

- such as cyclohexane, n-propyl cyclohexane, and the like;

are dimethyl formamide and the like.

The process of this invention is conducted, generally, under atmospheric pressures, although, if desired, the reaction can be conducted under subatmospheric or superatmospheric pressure.

sired temperature.

- instantaneous in that some isomaleimide is formed im- 6 The process of the present invention is conducted by simply admixing the reactants, in any order, at the de-- The reaction involved is practically mediately upon admixing of the reactants. Usually, however, the reaction mixture is allowed to stand for at least about one hour in order to insure that the reaction has proceeded to completion.

Recovery of the N-substituted isomaleimide from the reaction mixture can be accomplished by any one of a number of convenient methods, for example, by subjecting the reaction mixture to filtration, distillation, evaporation, or any combination of the three, depending upon the nature of the N-substituted isomaleimide produced. If desired, the N-substituted isomaleimide, after removal from the reaction mixture, can be washed with water or with an aqueous. solution of sodium bicarbonate, can be taken up by an organic diluent and passed through a Florisil column, or if a solid, it can be recrystallized fromsuitable solvents, such as the organic liquids previously noted in this specification as organic diluents.

The N-substituted maleamic acid intermediates which can be used in the preparation of the corresponding isomaleimides of the present invention can be obtained by reacting, in suitable solvents, approximately equimolar quantities of a primary monoor primary diamine with maleic anhydride. In producing an N-substituted maleamic acid having the formula previously given wherein R' is a monovalent hydrocarbon radical, the following primary mono-amines can be used: methylamine, ethylamine, isopropylamine, n-butylamine, isobutylamine, isoamylamine, n-hexylamine, n-heptylamine, n-octylamine, n-dodecylamine, cyclohexylaminc, 2-chloroethylamine, 2-bromoethylamine, 2-fluoroethylamine, 2-iodopropylamine, chlorocyclohexylamine, methoxymethylamine, 2- phenoxy-n-propylamine, benzylamine, 2-phenethylamine, S-phenyl-n-propylamine, 4-phenyl-n-butylamine, naphthylamine, p-toluidine, o-p-xylylidine, o-ethylaniline, methylaniline, p-ethylaniline, o-isopropylaniline, m-ism propylaniline, p-isopropylaniline, o-n-butylaniline, m-nbutylaniline, p-n-butylaniline, p-n-octylaniline, o-chloroaniline, m-bromoaniline, p-fluoroaniline, o-iodoaniline, o-methoxyaniline, m-methoxyaniline, pethoxyaniline, p-n-butoxyaniline, o-nitroaniline, p-nitroaniline, 4-chloro- 3-methylaniline, o-toluidine, m-toluidine, 4-sulfamylaniline, and the like.

In producing an N-substituted maleamic acid having the formula previously given wherein R is a divalent hydrocarbon radical, the following primary diamines can be used: 1,2-diaminoethane, 1,3-diamino-n-propane, 1,4-diamino-n-butane, 1,5-diamino-n-pentane, 1,6-diamino-n-hexane, 1,10-diamino-n-decane, 1,4-phenylene diamine, 4,4'-diamino-diphenylmethane, and the like. Process for producing maleamic acids is further described in the book Maleic Anhydride Derivatives by L. A. Flett and W. H. Gardner, which is incorporated hercin by reference.

The N-substituted isomaleimides of the present invention can be used as fungicides and defoliants. These compounds can also be isomerized to the corresponding maleimides which are known compounds having utility as insecticides. The so-called bis-isomaleimides of the present invention have particular utility in that they can be polymerized with primary diamines to produce polymers which can be molded into various articles, such as lamp bases, television cabinets, and the like, as well as extruded into film material which can be used as wrapping material for food articles, such as bread, meat, and the like. Moreover, these polymers can be cross-linked with sulfur to form infusible, insoluble products.

The following examples further illustrate the present invention and are not intended to limit the scope thereof in any manner.

' pressure.

7 EXAMPLE 1 Preparation of N-phenyl isomaleimide Into a dry, round bottom Pyrex glass flask equipped with a stirrer, thermometer, dropping funnel, and reflux condenser there was charged 50 ml. of dichloromethane having 10 grams (0.05 mole) of N-phenyl maleamic acid dissolved therein. To this solution there was then added. 10 grams (0.1 mole) of triethylamine. 'Ihe flask was then placed in an ice bath andwhile there 11 grams (0.44 mole) of trifluoroacetic anhydride were added dropwise into the flask. The reaction mixture was then allowed to stand for 16 hours at room temperature, about 25 C. After 16 hours, the dichloromethane was evaporated from the mixture under reduced The solid residue was treated with successive portions (100 ml.) of water and dichloromethane in a separatory funnel. The dichloromethane in which there was dissolved the solid residue was separated from the water layer and dried over magnesium sulfate. The dichloromethane was removed under reduced pressure and the residue dissolved in benzene. The benzene solution was passed through a Florisil column which had been prepared in benzene. The eluant, when evaporated, yielded 4.5 grams of a crystalline solid having a melting point of 58 C.-60 C. The product was identified as N-phenyl isomaleimide by infra-red spectrum analysis. The infra-red spectrum of the product contained bands at 5.6 and 5.8 1. which are consistent with the isomaleimide structure.

EXAMPLE 2 Preparation of N-n-butyl isomaleimide Into a dry, round bottom, Pyrex glass tube equipped with a stirrer, thermometer, dropping funnel, and reflux condenser there was charged a solution of 17.3 grams (0.18 mole) of N-n-butyl maleamic acid and 20.2 grams (0.47 mole) of triethylamine in 200 ml. of benzene. To this solution there was added 17 grams (0.1 mole) of chloroacetic anhydride. The reaction mixture was heated at reflux, about 80 C., for two hours and then allowed to cool to about room temperature. The solution was then washed with 100 ml. of water, the organic layer recovered, and distilled whereby the benzene was removed. The residue was distilled at 55 C.-60 C. at a pressure of 0.5 mm. Hg yielding as the distillate a clear liquid. This product was identified as N-n-butyl isomaleimide by infra-red analysis. The infra-red spectrum shows bands at 5.5;/. and 5.90p which are consistent with the isomaleimide structure.

What is claimed is:

1. Process for the preparation of an N-substituted ism maleimide which comprises admixing an N-substituted maleamic acid having the formula:

wherein R is a member selected from the group consisting of a monovalent hydrocarbon radical, and a divalent hydrocarbon radical having as a substituent on its terminal carbon atom a radical having the formula:

with at least a stoichiometric amount of a acid-anhydride having the formula:

wherein R and R are alkyl radicals, each having at least on halogen atom attached to its a carbon atom, and with at least a stoichiometric amount of an organic tertiary amine, for a period of time sufiicient to produce the corresponding N-substituted isomaleimide.

2. Process as defined in claim 1 wherein the N-substituted maleamic acid is N-phenyl maleamic acid.

3. Process as defined in claim 1 wherein the N-substituted maleamic acid is N-n-butyl maleamic acid.

4. Process as defined in claim 1 wherein the halogenated acid anhydride is trifluoroacetic anhydride.

5. Process as defined in claim 1 wherein the organic tertiary amine is triethylamine.

6. Process as defined in claim 1 wherein the reacting materials are admixed at a temperature from about ---70 C. to below the decomposition temperature of the reactants and of the N-substituted isomaleimide formed.

7. Process as defined in claim 1 wherein the reacting materials are admixed at a temperature of'from about 5 C. to about 85 C.

8. Process for the preparation of an N-substituted isomaleimide which comprises admixing in an organic diluent and at a temperature of from about -5 C. to about 85 C. an N-substituted maleamic acid having the formula:

halogenated H-C-ii-OH H-C-GNR' I 1. wherein R is a member selected from the group consisting of a monovalent hydrocarbon radical and a divalent hydrocarbon radical having as a substituent on its terminal carbon atom a radical having the formula:

with a stoichiometric amount of a halogenated acid anhydride having the formula:

wherein R and R are alkyl radicals, each having at least one halogen atom attached to its a carbon atom, and with a stoichiometric amount of an organic tertiary amine, for a period of time sufiicient to produce the corresponding N-substituted isomaleimide.

9. Process as defined in claim 1 wherein the halogenated acid anhydride is chloroacetic anhydride.

References Cited in the file of this patent Piutti: Gazz. Chim Ita1., vol. 40 (XL), pp. 488 and 508-515 (1910).

Tsou et. a1.: I. Am. Chem. Soc., vol. 77, pp. 4613- 4616 (1955).

Roderick: I Am. Chem. Society, vol. 79, pages 1710- 12 (1957). 

1. PROCESS FOR THE PREPARATION OF AN N-SUBSTITUTED ISOMALEIMIDE WHICH COMPRISES ADMIXING AN N-SUBSTITUTED MALEAMIC ACID HAVING THE FORMULA: 